Increased expression of Myosin binding protein H in the skeletal muscle of amyotrophic lateral sclerosis patients
Increased expression of Myosin binding protein H in the skeletal muscle of amyotrophic lateral sclerosis patients
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DOI：
10.1016/j.bbadis.2013.10.013
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发表时间：
2014-01-01
影响因子：
6.2
通讯作者：
Alessio, Massimo
中科院分区：
文献类型：
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作者：
Conti, Antonio;Riva, Nilo;Alessio, Massimo
肌萎缩侧索硬化症（amyotrophiclateralsclerosis，ALS）是一种严重的致死性神经退行性疾病，其发病机制尚不清楚.最近的研究表明，骨骼肌可能发挥积极的致病作用。为了研究ALS的发病机制和寻找诊断标志物，我们用差异表达蛋白质组学方法分析了骨骼肌活检组织。我们研究了来自健康对照（CN）、散发性ALS（sALS）、运动神经病（MN）和肌病（M）的骨骼肌活检。在几种差异表达的蛋白质中，肌球蛋白结合蛋白H（MyBP-H）在ALS样品中的表达非常高。MyBP-H是骨骼肌粗肌丝的一种成分，对肌球蛋白有很强的亲和力，但其功能尚不清楚。MyBP-H高表达与Rho激酶2（ROCK 2）、LIM结构域激酶1（LIMK 1）和cofilin 2的异常表达有关，可能影响肌动蛋白-肌球蛋白相互作用。我们建议MyBP-H表达水平作为骨骼肌中的假定生物标志物，用于区分ALS和运动神经病，并且它发出肌动蛋白-肌球蛋白相互作用失调的信号;这反过来可能有助于ALS的发病机制。(C)2013爱思唯尔有限公司版权所有。
Amyotrophic lateral sclerosis (ALS) is a severe and fatal neurodegenerative disease of still unknown pathogenesis. Recent findings suggest that the skeletal muscle may play an active pathogenetic role. To investigate ALS's pathogenesis and to seek diagnostic markers, we analyzed skeletal muscle biopsies with the differential expression proteomic approach. We studied skeletal muscle biopsies from healthy controls (CN), sporadic ALS (sALS), motor neuropathies (MN) and myopathies (M). Pre-eminently among several differentially expressed proteins, Myosin binding protein H (MyBP-H) expression in ALS samples was anomalously high. MyBP-H is a component of the thick filaments of the skeletal muscle and has strong affinity for myosin, but its function is still unclear. High MyBP-H expression level was associated with abnormal expression of Rho kinase 2 (ROCK2), LIM domain kinase 1 (LIMK1) and cofilin2, that might affect the actin-myosin interaction. We propose that MyBP-H expression level serves, as a putative biomarker in the skeletal muscle, to discriminate ALS from motor neuropathies, and that it signals the onset of dysregulation in actin-myosin interaction; this in turn might contribute to the pathogenesis of ALS. (C) 2013 Elsevier B.V. All rights reserved.